Supplementary Material for: Efficacy and Safety of IL-17 and JAK Inhibitors in Ankylosing Spondylitis: A Systematic Review and Network Meta-Analysis

Objective: The aim of this study was to compare the clinical efficacy and safety of interleukin-17 inhibitors and Janus kinase inhibitors in the treatment of ankylosing spondylitis based on a network meta-analysis.
Methods: According to the search strategy, systematic retrievals were conducted in PubMed, Embase, Web of Science, the Cochrane Register of Clinical Trials, Scopus, and website ClinicalTrials.gov, from the establishment to December 8, 2023. Randomized controlled trials (RCTs) of interleukin-17 inhibitors and Janus kinase inhibitors for the treatment of ankylosing spondylitis were selected according to the inclusion and exclusion criteria. The included studies were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Software Stata 16.0, to compare the effectiveness and safety differences in all interventions.
Results: A total of 18 RCTs involving 3968 subjects were included in this study. The interventions were ranked from best to worst in terms of ASAS20: netakimab 120 mg > filgotinib 200 mg > tofacitinib 5 mg> brodalumab 210 mg >upadacitinib 15 mg >bimekizumab 160 mg > secukinumab 300 mg> ixekizumab 80 mg Q4W > secukinumab 150 mg > secukinumab 150 mg no LD> placebo, netakimab 120 mg outperformed all other interventions and the difference was statistically significant. The interventions were ranked from best to worst in terms of ASAS40: netakimab 120 mg > tofacitinib 5 mg > secukinumab 150 mg > secukinumab 300 mg > upadacitinib 15 mg > bimekizumab 160 mg> ixekizumab 80 mg Q4W > filgotinib 200 mg > brodalumab 210 mg > secukinumab 150 mg no LD > placebo, netakimab 120 mg outperformed all other interventions and was statistically significant (except the intervention of filgotinib 200 mg). In terms of AEs and SAEs, there was no statistical significance among all interventions.
Conclusions: The results of the network meta-analysis showed that netakimab 120mg ranked relatively high in outcome of ASAS20 and ASAS40. All treatments with IL-17 and JAK inhibitors were generally safe and well tolerated. However, the two included netakimab clinical studies may have limitations. Therefore, the therapeutic agents should be carefully selected in clinical treatment. Moreover, the efficacy and safety of netakimab remain to be further analyzed in studies with larger sample sizes and longer follow-up times.

研究目的：本研究旨在基于网状meta分析（network meta-analysis），比较白细胞介素-17抑制剂（interleukin-17 inhibitors）与Janus激酶抑制剂（Janus kinase inhibitors）治疗强直性脊柱炎（ankylosing spondylitis）的临床疗效与安全性。
研究方法：按照预设检索策略，于各数据库建库至2023年12月8日期间，在PubMed、Embase、Web of Science、Cochrane临床对照试验注册库（Cochrane Register of Clinical Trials）、Scopus及ClinicalTrials.gov网站开展系统检索。根据纳入与排除标准，筛选白细胞介素-17抑制剂与Janus激酶抑制剂治疗强直性脊柱炎的随机对照试验（randomized controlled trials, RCTs）。采用Cochrane偏倚风险评估工具对纳入研究进行质量评价，并通过Stata 16.0软件完成统计学分析，以比较各干预措施间的疗效与安全性差异。
研究结果：本研究共纳入18项随机对照试验，涉及3968名受试者。以ASAS20为疗效结局指标时，各干预措施从优至劣排序为：奈妥珠单抗120mg（netakimab 120 mg）＞非戈替尼200mg（filgotinib 200 mg）＞托法替布5mg（tofacitinib 5 mg）＞布罗达单抗210mg（brodalumab 210 mg）＞乌帕替尼15mg（upadacitinib 15 mg）＞比美吉单抗160mg（bimekizumab 160 mg）＞司库奇尤单抗300mg（secukinumab 300 mg）＞依奇珠单抗80mg 每4周一次（ixekizumab 80 mg Q4W）＞司库奇尤单抗150mg（secukinumab 150 mg）＞无负荷剂量司库奇尤单抗150mg（secukinumab 150 mg no LD）＞安慰剂（placebo），其中奈妥珠单抗120mg的疗效显著优于其余所有干预措施，且差异具有统计学意义。以ASAS40为疗效结局指标时，各干预措施从优至劣排序为：奈妥珠单抗120mg＞托法替布5mg＞司库奇尤单抗150mg＞司库奇尤单抗300mg＞乌帕替尼15mg＞比美吉单抗160mg＞依奇珠单抗80mg Q4W＞非戈替尼200mg＞布罗达单抗210mg＞无负荷剂量司库奇尤单抗150mg＞安慰剂，奈妥珠单抗120mg的疗效显著优于其余所有干预措施，且差异具有统计学意义（非戈替尼200mg组除外）。在不良反应（adverse events, AEs）与严重不良反应（serious adverse events, SAEs）方面，各干预措施间未观察到统计学差异。
研究结论：本网状meta分析结果显示，奈妥珠单抗120mg在ASAS20与ASAS40结局指标中均表现优异。所有白细胞介素-17抑制剂与Janus激酶抑制剂类治疗药物总体安全性良好，耐受性佳。但本研究纳入的两项奈妥珠单抗临床研究或存在局限性，因此临床治疗中需谨慎选择治疗方案。此外，奈妥珠单抗的疗效与安全性仍需在大样本量、更长随访周期的研究中进一步验证。